viral infection of the skin & mucous membrane

Viral infection of the skin & mucous membrane

Dr Mohammed ArifAssociate professor Consultant virologistHead of the virology unit, college of medicine & KKUH

Viral infection of the skin & mucous membrane

Viral diseases associated with maculopapular rash. Viral disease associated with vesicular rash. Human warts.

Macules : flat, red spots . Papules : slightly raised spot from the skin, but do not

contain fluids . The virus is not shed from the lesions of the

maculopapular rash .

Viral diseases associated with maculopapular rash

Measles. Rubella (German measles), Erythema infectiosum (slapped cheek or fifth disease). Exanthem subitum (roseola infantum or sixth disease).

Measles

Viral etiology : measles virus. Family : paramyxoviridae, Enveloped, with two glycoprotein spikes. Hemagglutinine spikes are the main neutralizing Ag. Also mediate adsorption of the virus to the host cell

surface.

Structure & classification (cont.)

The F-glycoproteins, mediate penetration of the virus to the host cell by fusion process and mediate fusion of infected cells together to form multinucleated giant cell (syncytium formation).

Helical nucleocapsid . The viral genome is SS-RNA, with negative polarity. Virion contains the enzyme transcriptase. One antigenic serotype.

Measles virus

Measles

Transmission : by inhalation of respiratory droplets. IP : 10 – 14 days. Target group : children.

Pathogenesis

After entry, the virus replicates in the epithelial cells of the URT.

The virus then invades the sub-epithelial tissues and reaches the lymphatic system and the blood stream .

The virus then spreads by blood and infects the endothelial cells of the blood vessels.

The cytotoxic T-cells attack virus infected vascular endothelial cells. And this will lead to the development of the maculopapular rash.

Clinical features

Prodromal : Fever, cough, mild conjunctivitis, nasal discharge. Lasting1-3 days.

Koplik's spots : small, red papules with white central dot, appear on the side of the cheek, their number 5 or 6, remain for a day or two. They are diagnostic for measles.

Rash : maculopapular rash, first appear on the face then spread downward over the trunk and extremities.

Clinical features (cot,)

The rash is red, become confluent, last 4 or 5 days, then disappears leaving brownish discoloration of the skin and fine desquamation.

Recovery is usual.

Complications

Common complications: croup, bronchitis , otitis media.

Rare complications : post-infectious encephalomyelitis, Sub acute sclerosing pan encephalitis (SSPE) & giant cell pneumonia.

Koplik’s spots

Clinical features of measles

Measles

Measles

Measles

Post infectious encephalomyelitis

Rare complication of measles. Develops few days of the main illness. Symptoms are : fever, headache, vomiting,

drowsiness, mental confusion, lack of coordination, convulsions.

Survivors are left with permanent neurological sequalae.

It is an auto immune disease, in whish the immune system attacks neurons.

SSPE

Late and rare complication of measles. Due to reactivation of mutant measles virus, latent in

the brain. Develops several years after measles attack. The disease is characterized by personality changes,

memory defect, impairment of vision speech and cognition, lack of coordination, blindness, convulsion, coma & death.

No effective treatment.

SSPE

Diagnosis is based on the clinical features, characteristic EEG and high level of measles Ab in the CSF.

Giant cell pneumonia

Rare complication. Seen in the immunocompromised children. Due to direct virus invasion of the lungs.

Prevention

Live attenuated vaccine (MMR). Contains live attenuated measles, mumps and rubella

virus strains. Administered in one dose. Protection; good immunity. Contraindications: should not be given to pregnant

women and immunocompromized.

Treatment & lab. diagnosis

Treatment: there is no specific anti viral drug therapy. Lab. Diagnosis : By detection of IgM-Ab to measles

virus.

Rubella (German measles)

Viral etiology: Rubella virus. Family :Togaviridae. Genus : Rubivirus. The virus is enveloped, pleomorphic with icosahedral

nucleocapsid. The viral genome is SS-RNA with positive polarity.

Rubella

Transmission :By inhalation of respiratory droplets. IP : 14 – 21 days. Target group : children.

Pathogenesis

After entry, the virus replicates in the epithelial cells lining the URT and invades sub-epithelial tissue.

The virus spreads by the blood stream to lymphoid tissues, followed by viremia.

The virus infects the endothelial cells of blood vessels in the skin, leading to the development of the maculopapular rash.

Virus-Ab complexes are thought to play a role in the development of the rash.

Clinical features

Prodromal : Fever, cough, nasal discharge, mild conjunctivitis.

Rash : Maculopapular rash, first appears on the face then spreads downwards to trunk and limbs.

The rash is red, discrete, usually fades after 48 hr. In nearly 50% of all infections there is no rash at all. Rubella is characterized by enlargement of the post-

auricular and sub-occipital lymph nodes.

Complications

Mild arthritis in adult females. Post infectious encephalomyelitis. Thrombocytopenic purpura.

Clinical features of rubella

Rubella

Rubella

Prevention , treatment & lab Diagnosis.

Vaccine : Live attenuated vaccine (MMR). Treatment : There is no specific viral therapy. Lab. Diagnosis : By detection of IgM-Ab rubella virus.

Congenital rubella

Infection occur in utero before rupture of the fetal membrane.

The fetus is infected transplacentally. Rubella virus has no cytocidal effect on the fetal cells, The virus establishes persistent infection in the fetal

cells. It interferes with cell division resulting in malformations in the heart, eyes and hearing organs.

Congenital rubella

Congenital rubella occurs when non-immune pregnant women acquires the virus in the first trimester of pregnancy.

The main congenital defects are: eye abnormalities, congenital heart diseases, deafness & mental retardation.

Affected infants have also hepatosplenomegaly, thrombocytopenic purpura, low birth weight, jaundice and anemia.

Congenital rubella

Infected infants shed the virus into throat and urine for several months and can infect susceptible individuals.

Prevention & lab. Diagnosis.

Prevention : By immunization of all children at age of 15-months with the MMR vaccine.

Lab Diagnosis : By detection of IgM-Ab to rubella virus in the infant serum.

Slapped cheek, Erythema infectiosum, Fifth disease.

Viral etiology: Human parvovirus B-19. Family: Parvoviridae. Small. Unenveloped, icosahedral, ss-DNA. One antigenic type. IP: 4-10 days. Transmission: By inhalation of respiratory droplets. Target group: children.

Pathogenesis

The virus infects two types of cells: The endothelial cells of the blood vessels in the skin. And the red blood cells precursors (erythroblast) in the

bone marrow, which account for aplastic anemia. Immunocomlexes may attribute to the development of

the rash and arthritis.

Clinical features

The disease starts with fever, sneezing and coughing. Followed by the development of the maculopapular

rash. The rash is red, confluent, fine, most intense on the

cheek. The rash may appear on the trunk and limbs. Lesions fades from the center leaving the periphery

red, developing characteristic reticular or lace like pattern.

Clinical features

There is mild generalized lymphadenopathy. Arthralgia with swelling and pain in the joints are seen

in women. Recovery is complete.

Clinical features of slapped cheek

Slapped cheek.

Complications

Aplastic anemia, absence of regeneration of blood cells , seen in the immunocompromized .

Transient aplastic crisis, sudden and temporary disappearance of erythroblasts from the bone marrow, seen in patients with hemolytic anemia.

The bone marrow does not manufacture RBC ( bone marrow suppression ) .

Prevention, treatment & lab. diagnosis

Prevention. There is no vaccine available yet.

Treatment. There is no specific antiviral drug therapy.

Lab, diagnosis. By detection of Ig-M antibody.

Fetal infection

Congenital infection due to parvovirus B-19 occurs when non immune pregnant women acquire the virus in the first half of pregnancy.

Intrauterine infection can lead to severe anemia, massive edema, congestive heart failure and fetal death (hydrops fetalis).

Exanthem subitum, Roseola infantum,Sixth disease

Caused by human herpes virus type-6. Family: herpesviridae. Enveloped, icosahedral, with ds-DNA genome. IP: 10-14 days. Transmission : By inhalation of respiratory droplets, Target group : Children.

Clinical features.

The disease starts with fever for 3-5 days. As the fever subsides a discrete maculopapular rash appears first on the trunk then spreads to face and limps.

There is a mild generalized lymphadenopathy. Recovery is complete. Complications: Rare, thrombocytopenia, encephalitis. Prevention: There is no vaccine available yet. Treatment: there is no specific anti-viral drug therapy.

Viral diseases associated with vesicular rash

HSV-1 infection. HSV-2 infection. Varicella (chickenpox). Zoster. Herpangina. Hand-foot & mouth disease.

Family : Herpesviridae.

All herpes viruses are morphologically identical and have the same structure.

They consist of outer envelope and internal nucleocapsid.

The capsid is icosahedral with 162-capsomeres. The viral genome is linear ds-DNA.

Typical structure of herpes viruses

Herpesviruses

There are eight human herpes viruses. Herpes simplex virus type-1 (HSV-1). Herpes simplex virus type-2 (HSV-2). Varicella –zoster virus (VZV). Cytomegalovirus (CMV). Epstein-Bar virus (EBV). Human herpes virus type 6 (HHV-6). Human herpes virus type 7 (HHV-7). Human herpes virus type 8 (HHV-8).

Classification

Three subfamilies. Alfa herpesvirinae, HSV-1, HSV-2, VZV. Beta herpesvirinae, CMV, HHV-6, HHV-7. Gamma herpesvirinae, EBV, HHV-8.

Latency

The most important characteristic of herpes viruses is latency.

After resolution of primary infection, the virus remains latent inside the human body for life.

HSV-1, remains latent in the trigeminal ganglion. HSV-2, remains latent in the sacral ganglion. VZV, remains latent in the dorsal root ganglion.

Types of HSV-1 infection

1--- Primary HSV-1 infection: Mostly inapparent, if there is a clinical manifestation,

it takes the form of: Gingivostomatitis. Pharyngotonsilitis. Herpetic whitlow. Keratoconjunctivitis. Encephalitis. Disseminated infection in the immunocompromised.

Types of HSV-1 infection

2--- Recurrent infection: Due to reactivation of latent virus in the trigeminal

ganglion. Two types of recurrent infections:

Herpes labialis. Keratitis.

Pathogenesis

After entry ,the virus replicates locally in the skin at the site of entry.

Typical herpes lesions are developed. The virus migrates up the neurons to the trigeminal

ganglion and remain latent. When the virus is reactivated, it travels through

neurons to the same site where primary infection occurred.

Latency in HSV-1 ( trigeminal ganglion).

HSV-1 Latency

Transmission

By direct contact with herpes lesions. By saliva.

Clinical features

1- Gingivostomatitis: Occurs primarily in children. The disease is characterized by: Fever, localized pain, vesicles develop on the buccal

mucosa and gums, vesicles ruptures to form ulcers. The disease is self limiting, recovery is usual. The virus remains latent in the trigeminal ganglion. The disease usually lasts for 5-12 days.

Gingivostomatitis

Gingivostomatitis

Clinical features

2- Herpetic whitlow: Vesicles and ulcers appear on the tips of the fingers. Affects nurses and dentist.

Herpetic whitlow

Herpetic whitlow

Herpetic whitlow

Clinical features

3- Kerato conjunctivitis: Primary infection can involve both conjunctiva and

cornea. Incase of conjunctivitis, there is localized pain, edema,

preauricular adenopathy, lacrimation, vesicles and ulcers appear on the conjunctiva.

Clinical features

Keratitis: Corneal infection varies from superficial that heal

without damage to one affecting deeper parts of the eye.

Severe ulceration of the cornea may lead to blindness, usually unilateral.

Symptoms include: severe eye pain, photophobia, blurred vision and intense lacrimation.

Clinical features

4- Encephalitis: A rare manifestation of primary HSV-1 infection. The virus invades directly the brain. Usually vesicles are not present on the body surface. The temporal lobes are primarily involved. The main symptoms are : fever, severe headache,

drowsiness, metal confusion, lack of coordination, convulsions.

Herpes encephalitis is usually caused by HSV-1 . Mortality rate is high, survivors are left with permanent

neurological sequalae.

Herpes encephalitis

Recurrent infections

1- Herpes labiales (cold sores) Usually milder disease, with short duration. Few vesicles usually appear around the lips.

2- Keratitis: Repeated ulceration of the cornea may lead to

blindness.

Herpes labialis

Herpes labialis

Gingivostomatitis

HSV-2

Types of infections: Primary infection --- Genital herpes. --- Neonatal herpes.

Recurrent infection --- Genital herpes.

Genital herpes

Both HSV-1 & HSV-2 can cause genital herpes. About 90% of genital herpes are caused by HSV-2

and only 10% by HSV-1. The signs and symptoms are similar in both cases.

Transmission

Sexually, by direct skin contact with herpetic lesions, vesicle fluid and vaginal secretions.

From infected mother to neonate (neonatal herpes) mainly perinatally (during labor and delivery).

HSV-2 infects sexually active adults, especially those with multiple sexual partners.

Pathogenesis

HSV-2 enters the body through the mucous membrane of the genitalia or through abraded or traumatized skin.

After entry, the virus replicate at the portal of entry. After resolution of primary infection, the virus travels

along the neurons to the sacral ganglion and remain latent for life.

The latent virus may reactivated under certain stimuli and recurrent herpetic infection occurs.

When the virus is reactivated, it travel backs from the sacral ganglion through nerve axons to the same site of primary infection.

Pathogenesis

The virus remains latent in an episomal form (plasmid).

During latency, no viral genes are expressed,

Primary genital herpes

Primary infection is usually asymptomatic. Symptomatic infection is characterized by: localized

pain, erythema, edema, inguinal lymph adenopathy, development of localized vesicular rash, vesicles ruptures to form ulcers.

Herpetic lesions appear on the external genitalia of males and females.

Lesions also appear inside vagina, urethra and cervix. After resolution of primary infection, the virus travels

from the genitalia via neurons to the sacral ganglion where it remains latent.

Genital herpes

Neonatal herpes

Rare condition and often fatal to the neonate. It occurs when the mother is shedding the virus in the

birth canal at the time of delivery. The neonate acquires the virus during the passage in

the birth canal. Since the neonate is not immune to HSV-2, the virus

spread to many organs such as lungs, liver and the CNS.

Neonatal herpes

Neonatal herpes may take the form of:1- Generalized infection: the virus disseminates through

the neonatal organs and often fatal. The clinical features include: hepatomegaly,

thrombocytopenia, pneumonia and encephalitis.2- Encephalitis: due to direct invasion of the brain, the

mortality rate is high.3- Cutaneous lesions: confined to the skin. Prognosis is

good.

Neonatal herpes

Recurrent infections

Recurrent genital herpes is usually mild and last for few days.

Usually few vesicles develop on the external genitalia,with mild local symptoms such as pain and itching.

Lesions usually lasts 2-5 days. The reactivated virus travels back from the sacral

ganglion through neurons to the genital areas.

Lab. diagnosis

Isolation of the virus in tissue culture, followed by identification of the virus.

Scraping from the base of the vesicles, direct IF. Detection of Ig-M antibody to HSV-2. Detection of the viral-DNA, using PCR. This method is

limited to life threatening conditions, such as encephalitis.

Prevention

There is no vaccine is available yet for HSV-2. Prevention measures, by practicing safer sex (having

one sexual partner).

Treatment

Acyclovir, 400mg thrice daily for 10-days. Famciclovir, 250 mg thrice daily for 5-days. Valaciclovir, 1g, twice daily for 10-days.

Varicella (chickenpox)

Caused by varicella-zoster virus (VZV). The virus is transmitted by inhalation of respiratory

droplets and by direct contact with the skin lesions. Varicalla is a common childhood disease.

Varicella: is the primary illness. Zoster: is the recurrent form of the disease.

Pathogenesis

After entry, the virus replicates in the epithelial cells of the URT.

The virus spread by blood stream to the skin, where the typical vesicular rash occurs.

Clinical features

IP : 14-21 days. The disease starts with, fever, malaise, cough,

headache, generalized vesicular rash. The rash first appears on the trunk, then spreads to

face and limbs. The rash appears in successive waves. Lesions progress from macules to papules to vesicles. Vesicles ruptures to form ulcers. The illness usually lasts for 4-7 days.

Complications

Post-infectious encephalomyelitis. Pneumonia in adults. Hepatitis. Myocarditis.

Clinical features of varicella

Varicella

Varicella

Vaccine

Live attenuated vaccine is available. Administered in one dose. Recommended for children 1-12 years, teenagers and

adult who have not the diseases.

Lab. diagnosis

Detection of Ig-M antibody. Scraping from the base of the vesicles.

Treatment

No anti-viral drug therapy is necessary for immunocompetent children.

Severe cases of chickenpox is treated with acyclovir.

Congenital varicella

Very rare. Most pregnant women have immunity to varicella, due

to previous exposure. Varicella in the first half of pregnancy is associated

with fetal abnormalities include: --- limb hypoplasia, muscular atrophy, optical

atrophy, chorioretinitis, mental retardation and skin lesions.

Neonatal varicella

If the mother acquired varicella more than 7-days before delivery, then the disease in the neonate is usually mild. The disease is modified by the passively acquired maternal antibody.

If the mother acquired varicella within 7-days of delivery, the neonate is likely to develop severe disease.

Zoster (shingles)

Zoster is localized unilateral vesicular rash. It is a disease of elderly. It is due to reactivation of VZV, which is latent in the

dorsal root ganglion.

Zoster

Zoster

Types of zoster

1- Thoracic zoster. Reactivation of virus latent in the dorsal root ganglion,

results in a segmental rash, extends from the mid of the back in a horizontal strip, round the side of the chest.

2- Ophthalmic zoster. Reactivation of virus latent in the trigeminal ganglion

results in a localized vesicular rash that involves the scalp, forehead, eye lids and may be cornea.

Types of zoster

3- Ramsay Hunt syndrome. Localized vesicular rash appears on the tympanic

membrane and the external auditory canal. Often there is a facial nerve palsy.

Zoster

Zoster

zoster

Complications

Meningitis. Encephalitis. Myelitis. Disseminated zoster in the immunocompromized.

Treatment

Acyclovir (zovirax), 800 mg,orally, five times daily for 5 to 7 days.

Famciclovir (Famvir), 500 mg, orally, three times daily for seven days.

Valacyclovir (valtrex), 1000 mg. orally, three times daily, for seven days.